The overall goals of this project are the elucidation of the molecular bases and physiological consequences of the genetic lesion responsible for the aldose-ketose isomerase deficiency diseases. This will be carried out in the following manner: (a) By determining the alignment of the cysteinecleavage peptide of normal glucosephosphate isomerase and obtaining the amino acid compositions, end terminal analyses and tryptic fingerprints of each peptide; (b) by comparing four new genetic variants of human glucosephosphate isomerase by isolation of each form and comparing its chemical, physical and catalytic properties with those of the normal enzyme. We will conduct a detailed study of the factors involved in regulating the expression of a new isozyme of triosephosphate isomerase in human lymphocytes undergoing blast transformation. We will initiate studies on the human phosphomannose isomerase which will involve a screening of various tissues for levels of the enzyme and develop an isolation procedure for the enzyme. Finally, the project will study the hybridization and subunit-subunit interactions of normal, genetically- and chemically-modified forms of triosephosphate and glucosephosphate isomerases. BIBLIOGRAPHIC REFERENCES: Gracy, R.W., Nature of the Multiple Forms of Glucosephosphate Isomerase, Isozymes I - Molecular Structure (C.L. Markert, ed.) Academic Press, Inc., New York, 1975, PP. 471-487. Gracy, R.W., Triosephosphate Isomerase from Human Erythrocytes, Methods in Enzymology 41, 442-447 (1975).